The acute and chronic effects of the narcotic treatment agonists l-alpha-acetylmethadol and propoxphene napsylate and the narcotic antagonist naltrexone will be studied. Both narcotic tolerant and non-tolerant animals will be used except in the case of naltrexone, which will be administered in a sustained-release polylactic/glycolic acid copolymeric bead to non-tolerant animals only. We will study 3 hepatic metabolic functions: 1. The hepatic, microsomal mixed function oxidase system responsible for the metabolism of many drugs and endogenous steroids will be studied following acute and chronic administration of these 3 drugs. The activities of aminopyrine N-demethylase and aniline hydroxylase, respresenative type I and type II enzymes, and levels of cytochrome P450 will be monitored. Interactions, both in vitro and in vivo, between the above treatment drugs and representative type I and type II drugs will be studied. We shall also look at the activities responsible for biotransformation of these 3 drugs. 2. The effects of chronic administration of these drugs on the activity of the rate-limiting enzyme in heme metabolism, delta-aminolevulate synthetase, will be investigated. 3. The consequences of long-term administration of these drugs on the enzyme activities that irreversibly inactivate testosterone and progesterone, hepatic, microsomal and cytosolic 3-ketosteroid delta 4-reductases, will be assessed. In addition, the effects these drugs may have on the observed diurnal rhythms of these delta 4-reductase activities will be investigated.